Activation of a G-protein coupled receptor by conjugated bile acids in primary hepatocytes and liver: effects on glucose metabolism

2007 ◽  
pp. 11-19
Author(s):  
P. B. Hylemon ◽  
Y. Fang ◽  
E. Studer ◽  
W. M. Pandak ◽  
P. Dent
Keyword(s):  
Glucose Metabolism ◽  
Bile Acids ◽  
G Protein ◽  
Primary Hepatocytes ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Conjugated Bile Acids

scholarly journals Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

2019 ◽  
Vol 316 (5) ◽  
pp. G574-G584 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Samuel Addison Jack Trammell ◽  
Nicolai Jacob Wewer Albrechtsen ◽  
Kristina Schoonjans ◽  
Reidar Albrechtsen ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Peptide Yy ◽  
Whole Body ◽  
Rat Colon ◽  
G Protein Coupled Receptor ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion.NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.

scholarly journals A G Protein-coupled Receptor Responsive to Bile Acids

2003 ◽  
Vol 278 (11) ◽  
pp. 9435-9440 ◽  
Author(s):  
Yuji Kawamata ◽  
Ryo Fujii ◽  
Masaki Hosoya ◽  
Masataka Harada ◽  
Hiromi Yoshida ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals A Novel G-Protein Coupled Receptor Responsive to Bile Acids Regulates Intestinal Motility

2011 ◽  
Vol 140 (5) ◽  
pp. S-99
Author(s):  
Farzad Alemi ◽  
Daniel P. Poole ◽  
Jonathan Chiu ◽  
Cody B. Godfrey ◽  
Kristina Schoonjans ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Intestinal Motility ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus

2019 ◽  
Vol 116 (21) ◽  
pp. 10525-10530 ◽  
Author(s):  
James Meixiong ◽  
Chirag Vasavda ◽  
Solomon H. Snyder ◽  
Xinzhong Dong
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Sensory Neurons ◽  
G Protein Coupled Receptor ◽  
Humanized Mouse ◽  
Chronic Itch ◽  
Targeted Expression ◽  
Acute Injection ◽  
G Protein Coupled

Patients suffering from cholestasis, the slowing or stoppage of bile flow, commonly report experiencing an intense, chronic itch. Numerous pruritogens are up-regulated in cholestatic patient sera, including bile acids (BAs). Acute injection of BAs results in itch in both mice and humans, and BA-modulating therapy is effective in controlling patient itch. Here, we present evidence that human sensory neuron-expressed Mas-related G protein-coupled receptor X4 (MRGPRX4), an orphan member of the Mrgpr family of GPCRs, is a BA receptor. Using Ca2+ imaging, we determined that pathophysiologically relevant levels of numerous BAs activated MRGPRX4. No mouse Mrgpr orthologs were activated by BAs. To assess the in vivo relevance of BA activation of MRGPRX4, we generated a humanized mouse with targeted expression of MRGPRX4 in itch-encoding sensory neurons. BAs activated MRGPRX4+ sensory neurons at higher levels compared with WT neurons. Compared with control animals, MRGPRX4+ mice scratched more upon acute injection of BAs and in a model of cholestatic itch. Overall, these data suggest that targeting MRGPRX4 is a promising strategy for alleviating cholestatic itch.

scholarly journals Bile acids and ceramide overcome the entry restriction for GII.3 human norovirus replication in human intestinal enteroids

2020 ◽  
Vol 117 (3) ◽  
pp. 1700-1710 ◽  
Author(s):  
Kosuke Murakami ◽  
Victoria R. Tenge ◽  
Umesh C. Karandikar ◽  
Shih-Ching Lin ◽  
Sasirekha Ramani ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Early Stage ◽  
Age Groups ◽  
Acid Sphingomyelinase ◽  
Farnesoid X Receptor ◽  
Apical Surface ◽  
G Protein Coupled Receptor ◽  
Endosomal Acidification ◽  
G Protein Coupled

Human noroviruses (HuNoVs) cause sporadic and epidemic outbreaks of gastroenteritis in all age groups worldwide. We previously reported that stem cell-derived human intestinal enteroid (HIE) cultures support replication of multiple HuNoV strains and that some strains (e.g., GII.3) replicate only in the presence of bile. Heat- and trypsin-treatment of bile did not reduce GII.3 replication, indicating a nonproteinaceous component in bile functions as an active factor. Here we show that bile acids (BAs) are critical for GII.3 replication and replication correlates with BA hydrophobicity. Using the highly effective BA, glycochenodeoxycholic acid (GCDCA), we show BAs act during the early stage of infection, BA-dependent replication in HIEs is not mediated by detergent effects or classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling but involves another G protein-coupled receptor, sphingosine-1-phosphate receptor 2, and BA treatment of HIEs increases particle uptake. We also demonstrate that GCDCA induces multiple cellular responses that promote GII.3 replication in HIEs, including enhancement of 1) endosomal uptake, 2) endosomal acidification and subsequent activity of endosomal/lysosomal enzyme acid sphingomyelinase (ASM), and 3) ceramide levels on the apical membrane. Inhibitors of endosomal acidification or ASM reduce GII.3 infection and exogenous addition of ceramide alone permits infection. Furthermore, inhibition of lysosomal exocytosis of ASM, which is required for ceramide production at the apical surface, decreases GII.3 infection. Together, our results support a model where GII.3 exploits rapid BA-mediated cellular endolysosomal dynamic changes and cellular ceramide to enter and replicate in jejunal HIEs.

Tu1296 BILE ACIDS DELAY THE WOUND HEALING OF COLONIC EPITHELIAL CELL THROUGH TRANSMEMBRANE G-PROTEIN-COUPLED RECEPTOR 5

2020 ◽  
Vol 158 (6) ◽  
pp. S-1047-S-1048
Author(s):  
Yuka Azuma ◽  
Kazuhiko Uchiyama ◽  
Mariko Kajiwara ◽  
Satoshi Sugino ◽  
Hiroaki Kitae ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cell ◽  
Bile Acids ◽  
G Protein ◽  
Colonic Epithelial Cell ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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